ABSTRACT
Background: Pilonidal disease is a chronic inflammatory skin disorder typically located in the gluteal cleft. Treatment varies from antibiotic therapy to extensive surgical resection and reconstruction; however, complications and recurrence are common. To understand risk factors, outcomes, and costs associated with various treatments, we performed a retrospective chart review of all patients treated for pilonidal disease at a single health care system from 2008 to 2018. Methods: Patients with an ICD diagnosis code associated with pilonidal disease were identified. Charts were reviewed for demographic, clinical, and cost information related to pilonidal disease encounters. Data were analyzed for risk of recurrence by Cox proportional hazards regression and economic burden by Wilcoxon signed-rank test. Results: During the study time frame, 513 patients were diagnosed with pilonidal disease. Primary treatment included 108 patients (21%) with wide excision, 167 (32%) with antibiotics alone, 79 (15%) with incision and drainage, and 109 (21%) with incision and drainage plus antibiotics. The rate of recurrence following antibiotic therapy, incision and drainage, or wide excision was 36.7%, 35.9%, and 21.3%, respectively. Sex, body mass index, obesity, or hidradenitis suppurativa was not associated with recurrence; however, smokers who underwent incision and drainage had a higher risk of recurrence (Pâ¯<â¯.0001). The median cost of each primary treatment was $3,093 for excision, $607 for incision and drainage, $281 antibiotics alone, and $686 for incision and drainage plus antibiotics. Conclusion: Pilonidal disease presents with a high degree of heterogeneity and is often managed primarily with antibiotics, incision and drainage, or surgical excision. Risk of recurrence was less in patients who underwent wide excision; however, these patients had higher overall cost compared to patients that had nonoperative management. Level of evidence: Level III.
ABSTRACT
Although tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy in advanced lung adenocarcinoma (LUAD) patients with pathogenic alterations in EGFR, most patients develop acquired resistance to these agents via mechanisms enabling the sustained activation of the PI3K and MAPK oncogenic pathways downstream of EGFR. The tumor suppressor protein phosphatase 2A (PP2A) acts as a negative regulator of these pathways. We hypothesize that activation of PP2A simultaneously inhibits the PI3K and MAPK pathways and represents a promising therapeutic strategy for the treatment of TKI-resistant LUAD. After establishing the efficacy of small molecule activators of PP2A (SMAPs) in a transgenic EGFRL858R model and TKI-sensitive cell lines, we evaluated their therapeutic potential in vitro and in vivo in TKI-resistant models. PP2A activation resulted in apoptosis, significant tumor growth inhibition, and downregulation of PI3K and MAPK pathways. Combination of SMAPs and TKI afatinib resulted in an enhanced effect on the downregulation of the PI3K pathway via degradation of the PP2A endogenous inhibitor CIP2A. An improved effect on tumor growth inhibition was observed in a TKI-resistant xenograft mouse model treated with a combination of both agents. These collective data support the development of PP2A activators for the treatment of TKI-resistant LUAD.
